Abstract
The aim of this study was to evaluate genetic and epigenetic variation of the genome in patients with sensitive pulmonary tuberculosis (PT) before and after treatment, under the effect of peptide bioregulator—Ala–Glu–Asp–Gly. In lymphocyte cultures from patients with sensitive primary PT were studied: total heterochromatin with differential scanning calorimeter; facultative heterochromatin (sister chromatid exchanges) with 5-bromdeoxyuridin and mutation (chromosome aberrations). We determined: there was an epigenetic alteration of functional parameters of the genome in PT before treatment. The level of heterochromatin decreased in the telomeric regions of chromosomes (in control it was high) and increased in the middle regions of chromosomes (in control it was reduced); there was a high level of somatic recombination; revealed an increase of the frequency of cells with chromosome aberrations. Has been revealed the ability of bioregulator (Ala–Glu–Asp–Gly) to normalize the altered genomic parameters in patients with PT. The results obtained in the study, which testify to the specific epigenetic variability of the genome in patients with the sensitive form of PT, in particular—the redistribution of heterochromatin from telomere to the medial regions of chromosome arms, high level of somatic recombination and increased frequency of chromosomal aberrations, can contribute to the early detection of PT, and also a bioregulator—Ala–Glu–Asp–Gly can be used to determine the effectiveness of the treatment and used to develop new therapies.
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Acknowledgements
This article is dedicated to the memory of Professor A.A. Prokofieva-Belgovskaya from her grateful students.
Funding
This research was supported by Shota Rustaveli National Science Foundation (SRNSF) [Grant Number DI-2016-39].
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TL carried out the study and drafted the manuscript with TJ and JM. TB and MG were responsible for lymphocyte cultures and took part in the design of the study. NK and KR were responsible for the material collection parts. All authors were involved in finalizing the manuscript and read and approved the submitted version.
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Teimuraz Lezhava, Tamar Buadze, Tinatin Jokhadze, Jamlet Monaselidze, Maia Gaiozishvili, Ketevan Rubanovi and Nana Kiria confirm that this article content has no conflicts of interest.
Human and Animal Rights
Samples of peripheral blood were obtained from healthy individuals and from individuals with PT, after and before treatment. Biological material (peripheral blood) was collected out in accordance with international requirements, Research object-isolated lymphocytes for cultivation (in vitro). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain studies with animal subjects.
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Informed consent was obtained from all individual participants included in the study.
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Lezhava, T., Buadze, T., Jokhadze, T. et al. Normalization of Epigenetic Change in the Genome by Peptide Bioregulator (Ala–Glu–Asp–Gly) in Pulmonary Tuberculosis. Int J Pept Res Ther 25, 555–563 (2019). https://doi.org/10.1007/s10989-018-9699-4
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DOI: https://doi.org/10.1007/s10989-018-9699-4